Department of Physiology and Biomembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Group I metabotropic glutamate receptors (group I mGluRs; mGluR1 and mGluR5) exert diverse effects on neuronal and synaptic functions, many of which are regulated by intracellular Ca(2+). In this study, we characterized the cellular mechanisms underlying Ca(2+) mobilization induced by (RS)-3,5-dihydroxyphenylglycine (DHPG; a specific group I mGluR agonist) in the somata of acutely dissociated rat hippocampal neurons using microfluorometry. We found that DHPG activates mGluR5 to mobilize intracellular Ca(2+) from ryanodine-sensitive stores via cyclic adenosine diphosphate ribose (cADPR), while the PLC/IP(3) signaling pathway was not involved in Ca(2+) mobilization. The application of glutamate, which depolarized the membrane potential by 28.5±4.9 mV (n = 4), led to transient Ca(2+) mobilization by mGluR5 and Ca(2+) influx through L-type Ca(2+) channels. We found no evidence that mGluR5-mediated Ca(2+) release and Ca(2+) influx through L-type Ca(2+) channels interact to generate supralinear Ca(2+) transients. Our study provides novel insights into the mechanisms of intracellular Ca(2+) mobilization by mGluR5 in the somata of hippocampal neurons.

AMPA receptors, but not NMDA receptors, are responsible for glutamate-induced Ca2+ influx.

(A) The amplitudes of glutamate-induced Ca2+ transients (CaGlu) were significantly attenuated in Ca2+-free solutions. CaGlu was not affected by AP-5 (B), but was significantly decreased by the pretreatment with CNQX (C). (D) CaGlu was not inhibited by NASPM. (E) Bar graphs represent the ratio between first and second CaGlu. Scale bars indicate 10 sec (horizontal) and 50 nM (vertical). ** indicates p<0.01.